Fig. 2. Drugs that modulate channels of the TREK subfamily of K_2P channels and different binding sites identified. (a) Chemical formula of the most important activators for channels of the TREK/(TRAAK) subfamily. (b) Binding site of the 'NCA' BL-1249 mapped in the TREK-2 crystal structure template (PDB ID: 4XDJ) [48]. (c) ML402 bound in the 'cryptic' binding site of TREK-1 determined by a co-crystallization study (PDB ID: 6CQ9) [6]. (d) Binding site of norfluoxetine in TREK-2, see co-crystal structure PDB ID: 4XDL [5]. (e) Binding site of ruthenium red at the 'keystone' binding site, determined by co-crystallization with TREK-1^I110D (PDB ID: 6V3C) [58]. (f) Chemical formula of the most important inhibitors for channels of the TREK/TRAAK subfamily. (b-e) Potassium ions are represented by black spheres. Red arrows indicate the positions of the respective drugs in top view.